The present applicants were co-inventors of previous patent applications relating to novel spiro-derivatives of quinuclidine, see e.g. European Patent Appln. No. 0205247 A2, published Dec. 17, 1986, based on Israel Patent Applications Nos. 75166 filed May 10, 1985 and 77568 filed Jan. 10, 1986, and commonly assigned U.S. patent application Ser. No. 853,404 filed Apr. 18, 1986, the contents of which are incorporated herein by reference. These novel quinuclidine derivatives were found to possess central nervous system activity. The biological activity of the compound 2-methylspiro(1,3-oxathiolane-5',3)quinuclidine, which exists as geometrical cis- and trans-isomers depending upon whether the 2-methyl group is located on the same side of the oxathiolane ring as the quinuclidine ring nitrogen atom (cis) or on the other side of the quinuclidine ring nitrogen atom (trans), was in particular extensively investigated, and it was found on the basis of pre-clinical tests that the cis- compound could be especially promising for the control of senile dementia of Alzheimer's type (SDAT).
In addition to the existence of geometrical isomerism, the compounds in question also possess a potential for optical isomerism, as will be appreciated by those skilled in the art. As is also known, however, such a potential is not always readily realized in practice. Moreover, in view of the promise of the geometrical isomers of the compound 2-methylspiro(1,3-oxathiolane-5',3)quinuclidine for the treatment of SDAT, it is evidently of interest to know the relative biological activity of such compounds. The relationship between the direction of rotation of the plane of polarized light by a particular optical isomer on the one hand, and its biological potency on the other, is not predictable with any degree of certainty.
Therefore, it is a principal object of the invention to provide optical isomers of 2-methylspiro(1,3-oxathiolane-5',3)quinuclidine. Further objects of the invention, and especially those which relate to the provision of useful pharmaceutical compositions and methods for the treatment of disease in mammals, will be apparent from the description which follows.